S196: ELRANATAMAB, A B-CELL MATURATION ANTIGEN (BCMA)-CD3 BISPECIFIC ANTIBODY, FOR PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: EXTENDED FOLLOW UP AND BIWEEKLY ADMINISTRATION FROM MAGNETISMM-3
Authors: Mohamad Mohty, Michael H. Tomasson, Bertrand Arnulf, Nizar J Bahlis, Paula Rodríguez-Otero, Joaquín Martinez-Lopez, Cyrille Touzeau, Hang Quach, Julien Depaus, Hisayuki Yokoyama, Salomon Manier, Noopur Raje, Marc S. Raab, Emma Searle, Eric Leip, Sharon T. Sullivan, Akos Czibere, Andrea Viqueira, Alexander Lesokhin
Journal: HemaSphere (2023)

Background: MagnetisMM-3 (NCT04649359) is an open-label, multicenter, registrational phase 2 study evaluating the efficacy and safety of elranatamab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Aims: Results from the MagnetisMM-3 trial in patients naïve to BCMA-directed therapies (Cohort A) after >1 y of follow-up, including patients who switched from QW to Q2W elranatamab administration, are presented. Methods: Eligible patients were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody. Patients received SC elranatamab in 28-d cycles with step-up doses of 12 mg on C1D1 and 32 mg on C1D4 followed by 76 mg QW beginning C1D8. Patients treated for 6 cycles and achieving partial response (PR) or better with response persisting ≥2 mo were switched to 76 mg Q2W, 46 and 58 patients are included in the Q2W efficacy and safety analyses, respectively. Results: Overall, 123 patients received elranatamab. Median patient age was 68.0 y (range, 36−89), 63.4% of patients had an ECOG PS ≥1 and median prior lines of therapy was 5.0 (2−22); 96.7% and 42.3% of patients were triple-class- and penta-drug refractory, respectively. At data cutoff (~12 mo after last patient initial dose), the median follow up was 12.8 mo (0.2−22.7); 34.1% of patients remained on treatment. Most common reasons for permanent treatment discontinuation were progressive disease (39.0%) and adverse events (13.8%). Objective response rate per blinded independent central review (BICR) was 61% (95% CI 51.8−69.6), with 39 (31.7%) patients with complete response (CR) or stringent CR (sCR); very good partial response (VGPR) and PR were achieved in 29 (23.6%) and 7 (5.7%) patients, respectively. MRD-negativity (threshold 10–5) was achieved by 92.0% (n=23/25) of evaluable patients. Median duration of response (mDOR) has not been reached (95% CI 12.9−NE) and DOR at 12 mo was 74.1% (95% CI 60.5−83.6). In patients with CR/sCR or VGPR, mDOR was not reached by 12 mo; in patients with PR, mDOR was 5.2 mo (95% CI 1.6−NE). There were 46 responders by BICR who switched to Q2W dosing ≥24 wk prior to the data cut-off; among these patients, 80.4% maintained/improved their response ≥24 wk after the switch. Median progression-free and overall survival have not been reached by 12 mo, and the respective rates (95% CI) at 12 mo were 57.1% (47.2−65.9) and 62.0% (52.8−70.0). Most common Grade 3/4 treatment emergent adverse events were hematologic; Grade 3/4 non-hematologic events reported in ≥5% of patients were COVID-pneumonia (10.6%), hypokalemia (9.8%), pneumonia (7.3%), sepsis (6.5%), hypertension (6.5%), ALT increased (5.7%), and SARS-COV-2 test positive (5.7%). Among patients who switched to Q2W dosing, the incidence of Grade 3/4 AEs decreased by >10% after the switch. Summary/Conclusion Elranatamab remains efficacious and well tolerated in patients with RRMM after >1 y of follow-up. Updated analysis with a median follow up of ~15 mo, the longest of all phase 2 BCMA-CD3 bispecific antibody studies, including the outcome of patients who switched to the Q2W dosing, will be presented. These results support the continued development of elranatamab both as a monotherapy and in combination with standard or novel therapies for patients with MM. Keywords: Bispecific, Clinical trial, Multiple myeloma, B-cell maturation antigen